Preterm birth (PTB, birth prior to 37 weeks' gestation) is a leading cause of infant mortality. Of the known risk factors for PTB, among the strongest is African American (AA) race. Compared to Caucasians, AA women have more than 1.5 times the risk of PTB (16.8% vs. 10.5%). The proposed research will investigate whether specific bio behavioral factors linked to PTB influence the epigenetic regulation of genes to promote PTB in AA women. This research will contribute to a bio psychosocial understanding of within-race risk for PTB, providing insight into important risk and protective factors relevant to AA women. The proposed research is consistent with frameworks for eliminating racial disparities, which recognize the need to study risks within-race as a vital first step, and is congruent with the National Institute of Minority Health and Health Disparities goal of promoting understanding of the biological mechanisms involved in conditions that disproportionately affect health disparity populations. To evaluate the hypothesis that epigenetic mechanisms mediate the relationship between specific bio behavioral factors and PTB for AA women, the proposed study will leverage bio behavioral and biologic data from an on-going longitudinal study of preterm birth in AA women (R01 NR014800) that is enrolling a socioeconomically diverse cohort of H 960 pregnant AA women and collecting data during prenatal care appointments (at 10-14 and 26-30 weeks' gestation) and at delivery. Using a nested case-control approach, cases are designated as those who experience PTB (an estimated 125 cases) and controls as those who experience a term birth. Building from this study design, we will: (1) characterize PBMC DNA methylation and RNA expression patterns over the course of pregnancy among AA women who deliver preterm and at term; (2) identify bio behavioral factors - including nutritional status, stress, an reproductive tract infections - that influence patterns of peripheral DNA methylation and RNA expression; (3) evaluate associations between PTB and both DNA methylation and RNA expression among AA women that are independent of the bio behavioral factors and (4) determine whether these epigenetic differences can be detected in the second and/or third trimester. The success of this research is supported by a multidisciplinary collaboration of clinicians, basic and translational scientists representing expertise in obstetrical outcomes and maternal-child health, genetics and epigenetics, nutrition, stress, epidemiology and informatics; the overlap of key personnel for the proposed study and the on-going R01 'Bio behavioral Determinants of the Micro biome and Preterm Birth for Black Women'; and support from Emory University's Clinical and Translational Science Institute (CTSA award # NIH UL1TR000454). Finally, Atlanta is home to AA women of broad socioeconomic status who are served by Emory's affiliated delivery hospitals, allowing for sufficient variation in the bio behavioral factrs under study to distinguish independent and interactive effects on DNA methylation and, ultimately, on the risk of PTB.